Permissive and instructive causality: integrating biological and environmental factors in mental health.

Psychiatric disorders are complex conditions involving multifactorial, nonlinear causal dynamics, which make effective treatment challenging. To address this complexity, a framework is proposed that distinguishes between types of causality: permissive causality, which pertains to factors affecting the likelihood of an outcome occurring, and instructive causality, which refers to factors shaping the specific features of the outcome. In this framework, when considering an individual as a complex adaptive system, causal processes within the individual are permissive, whereas causal processes outside the individual can be either permissive or instructive in relation to the individual's global emergent outcomes. Accordingly, when dealing with mental states or complex behaviors, biological substrates - from genes to brain areas - operate through permissive causality, shaping a space of possibilities rather than instructing a specific outcome. By contrast, contextual factors - such as life challenges or subjective appraisal - can also operate through instructive causality, steering behavior and mental states toward specific trajectories. Therapeutic strategies should harness the synergistic interplay between these types of causality, targeting biological substrates to enable transitions in mental states, and leveraging contextual factors to steer these transitions toward mental well-being. Recognizing such interplay holds promise for developing innovative and effective approaches in precision psychiatry, especially for treatments enhancing plasticity - which itself operates through permissive causality - including antidepressants and psychedelics.